Infective endocarditis is still an important disease that accounts for 0.3-3.0/1000 of all hospital admissions and the viridans streptococci remain the most frequent cause of subacute bacterial endocarditis. In this group of streptococci, the nutritionally variant streptococci and S. mitis, account for 35-40% of the disease in man. To date, this is the first comprehensive analysis of the surface components of these strains. The overall objective of this research proposal is the continued systematic study of the subacute components of these two types of streptococci in order to better understand the interaction of these bacteria with the heart valve during the disease process. Toward this objective we plan to determine the identity of the antigen responsible for the protection observed using the rabbit endocarditis model. The cell wall polysaccharide, protein and ribitol teichoic acid are candidates for this function. Similar studies are planned for each of the NVS serotypes and strains of S. mitis. In addition, we will produce monoclonal antibodies against the serotype specific and the protective components to use in purification of these molecules and as specific probes for their structure. The serotype I amphiphile will be purified and characterized both chemically and serologically. These studies are also planned for serotype II and III strains. Furthermore, a serotyping scheme will be developed for strains of S. mitis followed by the chemical characterization of their cell wall. Finally the antibody response in patients with NVS and S. mitis endocarditis will be monitored using our purified bacterial components for their level of antibody. The knowledge gained from the proposed studies will permit the laboratory technician to isolate and rapidly identify the nutritionally variant streptococci from blood cultures, permit the antibiotic regimen to commence and continue for the proper period of time, and perhaps provide information for a potential vaccine against these groups of organisms for the population at risk. Infective endocarditis is a serious disease in that if not treated rapidly, secondary complications arise including renal and neurological damage. However, 60% of the deaths caused by this disease is due to congestive heart failure.